OBJECTIVES:

• Determine the toxicity of the combination of trastuzumab (Herceptin), paclitaxel, carboplatin, and gemcitabine in patients with HER2-overexpressing locally recurrent or metastatic urothelial carcinoma.
• Determine the complete and partial response rates in patients treated with this regimen.
• Determine the median and overall survival of patients treated with this regimen.

OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15; paclitaxel IV over 3 hours and carboplatin IV over 15 minutes on day 1; and gemcitabine IV over 30 minutes on days 1 and 8. Courses repeat every 3 weeks. Patients achieving a complete response (CR) receive 3 courses past CR. Patients achieving a partial response or stable disease continue on therapy until CR or disease progression or unacceptable toxicity.

Patients are followed for disease progression and survival. Patients with HER2-negative disease are not eligible for treatment but are followed every 6 months for response and survival.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 24 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed locally recurrent or metastatic urothelial carcinoma incurable by surgery or radiotherapy

  • Transitional cell OR squamous cell

• HER2 overexpression of the primary or metastatic site evidenced by 1 of the following:

  • 2+ or 3+ staining by immunohistochemistry
  • Positive FISH defined as greater than 2 with the Vysis system or greater than 4 with the Ventana system
  • Elevated serum HER2 greater than 16 ng/mL with the OSDI assay
• Biopsy-proven HER2 overexpression of metastatic site if primary site is histologically and serologically HER2 negative*

• Bidimensionally measurable or evaluable disease

  • Disease outside previously irradiated fields NOTE: *HER2-negative patients are not eligible for treatment but are followed for response and survival

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• SWOG 0-2

Life expectancy:

• More than 12 weeks

Hematopoietic:

• Granulocyte count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No significant cardiac disease
• Ejection fraction at least 50% by MUGA or 2D echocardiogram
• No evidence of symptomatic coronary artery disease
• No active ischemia on EKG
• No history of congestive heart failure

Other:

• No active bacterial infection
• No other prior malignancy except adequately treated basal or squamous cell skin cancer or carcinoma in situ
• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy for metastatic disease
• At least 6 months since prior adjuvant chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics